The basic objective of our laboratory effort has been, and continues to be, the characterization of basic developmental processes involved in normal craniofacial morphogenesis to enable identification of the causes of abnormal development. Our research strategy involves an approach to the etiology of congenital craniofacial dysmorphology from the standpoint of cellular and developmental biology. The rational elimination of teratogenic influences in human facial development requires a clear understanding of the biology of normal craniofacial ontogeny. Progress during the previous funding period has demonstrated that several molecular species (prostaglandins, catecholamines) shown to be present in the developing orofacial region, act in a receptor mediated fashion to modulate proliferation of embryonic palate mesenchymal cells by alteration of intracellular levels of cAMP. Studies outlined in the current application involve analysis of intracellular transduction mechanisms which mediate cAMP-induced biological responses to hormone and growth factor stimulation. We propose to investigate intracellular effectors (ornithine decarboxylase, cAMP-dependent protein kinase) by which secondary messengers (cAMP, Ca2+) evoke a developmentally significant biological response (growth, glycosaminoglycan synthesis) in embryonic palatal tissue.